Most preterm newborns are managed by ad hoc use phototherapy to reverse hyperbilirubinemia with the intent to prevent bilirubin neurotoxicity. A precise threshold-based relationship between specific total bilirubin levels and intervention has been elusive. This is most likely due to other biomarkers such as hemolysis, developmental maturation, concurrent illnesses, or even interventions, may impede bilirubin/albumin binding. The over- prescription of phototherapy has impacted clinical and family-centered care, and in the extreme preterm infants, it may have augmented their risk of mortality. Thus, the opportunity to precisely individualize phototherapy in order to reduce its prescription is unique. We have assembled a transdisciplinary team to examine critical unanswered questions including the postnatal role of bilirubin binding capacity (BBC) in the context of clinical modifiers and antecedents for a domain of recently reported bilirubin-induced neurologic disorders that includes neuro-anatomical, hearing, visual and developmental processing impairments. In this study, we will evaluate two new innovative nanotechniques to quantify bilirubin load for the first time in the context of a clinical decision algorithm to identify those most at risk for any bilirubn-related neurotoxicity. We anticipate that knowledge gained from this study will lead to ethically testable hypotheses to prescribe phototherapy with precision.